• Event-free survival after induction therapy [ Designated as safety issue: No ]
  
• Disease-free survival after maintenance therapy [ Designated as safety issue: No ]
  

• Complete remission (CR) rate after induction therapy [ Designated as safety issue: No ]
  
• Overall survival after induction therapy [ Designated as safety issue: No ]
  
• Toxicity after induction therapy [ Designated as safety issue: Yes ]
  
• Toxicity after maintenance therapy [ Designated as safety issue: Yes ]
  
• Probability of relapse and death in first CR after maintenance therapy [ Designated as safety issue: No ]
  
• Overall survival after maintenance therapy [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Compare the event-free and disease-free survival of older patients with acute myeloid leukemia, refractory anemia with excess blasts (RAEB), or RAEB in transformation treated with induction therapy comprising cytarabine in combination with two different doses of daunorubicin followed by cytarabine alone with or without post-induction therapy comprising gemtuzumab ozogamicin.

Secondary

• Compare the complete remission rate in patients treated with these regimens.
• Compare the overall survival of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Determine the probability of relapse and death during first complete remission in patients treated with post-induction gemtuzumab ozogamicin.
• Correlate prognostic factors (e.g., CD33 positivity, multidrug resistance phenotype, or cytogenetics) with probability of complete remission and overall, event-free, and disease-free survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and diagnosis (acute myeloid leukemia [AML] vs myelodysplastic syndromes [MDS]) for induction therapy. Patients are stratified according to participating center, diagnosis (AML vs MDS), induction treatment arm (I vs II), and response to induction therapy (complete remission [CR] vs no CR) for post-induction therapy.

• Induction therapy (course 1): Patients are randomized to 1 of 2 induction treatment arms.

  • Arm I: Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV over 3 hours on days 1-3.
  • Arm II: Patients receive cytarabine as in arm I and daunorubicin as in arm I but at a higher dose.

Approximately 28-35 days after the start of course 1 (or sooner if the bone marrow shows evidence of resistant disease), patients in both arms proceed to course 2 of induction therapy.

• Induction therapy (course 2): All patients receive cytarabine IV over 6 hours twice daily on days 1-6.

After completion of course 2, patients undergo assessment of remission status. Patients who do not achieve CR are removed from the study. Patients achieving CR proceed to post-induction therapy and undergo a second randomization.

• Post-induction therapy: Patients are randomized to 1 of 2 post-induction treatment arms.

  • Arm I: Patients receive no further chemotherapy.
  • Arm II: Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1, 29, and 57 in the absence of disease relapse or unacceptable toxicity. After completion of study treatment, patients are followed monthly for 1 year, every 3 months for 2 years, every 4-6 months for 2 years, and then periodically thereafter.

PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study within 4-5 years.